AB1130 CAUSAL ASSOCIATION BETWEEN LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND PSORIATIC ARTHRITIS
Authors: Q. Dong, X. Yang, M. Zhu, J. Y. Chen, Q. Feng, Q. Yu, P. F. He, X. Li, S. X. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Psoriatic arthritis (PsA) is an inflammatory disease that causes inflammation and swelling of the joints and entheses in addition to skin symptoms(PsA)[1]. Chronic psoriatic lesions may increase serum concentrations of low-density lipoprotein cholesterol (LDL-C) by producing large amounts of IL-6 and other pro-inflammatory cytokines, which release free fatty acids, cholesterol, and triglycerides from the adipose tissue[2]. However, whether LDL-C affects articular psoriasis is unclear. <h3>Objectives</h3> We used a two-sample Mendelian randomization (MR) analysis to investigate the causal associations of LDL-C with PsA. <h3>Methods</h3> Firstly, we obtained LDL-C-associated single-nucleotide polymorphisms (SNPs) from a GWAS published by the UK Biobank, including up to disequilibrium (LD) threshold for clumping was set to r<sup>2</sup> &lt; 0.001. The clumping window size was set to 10000 kb, and we selected autosomal biallelic SNPs with P-values &lt; 5 × 10<sup>-8</sup>. Thirdly, as for MR analyses, F statistics were calculated to evaluate the strength of each instrument, the F-statistic of each SNP&gt; 10, indicating a low risk of weak instrument bias. Inverse variance weighted (IVW) was the primary method to assess the association of genetically predicted LDL-C and PsA risk. Fourthly, MR-Egger and weighted median were applied to validate the results from IVW. The Cochrane Q test and funnel plots were used to test the possible heterogeneity. The directional pleiotropy was separated by intercepting from MR-Egger and MR-presso. Finally, a leave-one-out sensitivity analysis was also performed. <h3>Results</h3> With 158 LDL-C-associated SNPs, LDL-C was a hazard factor for PsA(OR =1.30,95%CI 1.02-1.65, P=0.032), which was consistent in direction with the weighted median(OR=1.38,95%CI,1.00-1.91, P=0.050) and MR-Egger(MR-Egger: OR=1.43, 95%CI 1.01-2.04, P=0.045). Heterogeneity existed in the results(P&lt;0.05). But IVW could provide a robust causal estimate in the presence of heterogeneity[3]. No evidence of pleiotropy was observed (MR-Egger-intercept: -0.0049, P=0.447), and leave-one-out sensitivity analysis showed that removing any SNP would not change the overall result, suggesting this finding was available. Details of the results were shown in Figure 1. <h3>Conclusion</h3> LDL-C was a hazard factor for PsA. Monitoring and lowering serum concentrations of LDL-C may make a difference in psoriasis treatment and slow down the process of PsA. <h3>References</h3> [1]Skornicki, Michelle et al. "Clinical Burden of Concomitant Joint Disease in Psoriasis: A US-Linked Claims and Electronic Health Records Database Analysis." <i>Advances in therapy</i> vol. 38,5 (2021): 2458-2471. doi:10.1007/s12325-021-01698-7 [2]Pietrzak, Aldona et al. "Serum concentration of interleukin 6 is related to inflammation and dyslipidemia in patients with psoriasis." <i>Postepy dermatologii i alergologii</i> vol. 37,1 (2020): 41-45. doi:10.5114/ada.2018.78028 [3]Chen, Lu et al. "No causal effect of tea consumption on cardiovascular diseases: A two-sample Mendelian randomization study." <i>Frontiers in cardiovascular medicine</i> vol. 9 870972. 7 Sep. 2022, doi:10.3389/fcvm.2022.870972 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.